Imagine you’re a fly buzzing through the forest looking for something to eat, and you happen upon a sweet fruit that tastes bitter. What’s a fly to do? A sweet fruit is a nutritious meal, but the bitter taste implies toxins. In a recent paper by French et al. in the Journal of Neuroscience, researchers discovered that bitter substances can block sugar signaling in the brain to prevent flies from making questionable meal choices such as these.

The brain deals with these sorts of ambiguities every day. After all, very few foods have a single taste modality of sweet, bitter, sour, salty, or umami (savory/meaty). Instead, most foods are a combination of several of these tastes. But while sweet, umami, and sometimes salt flavors can indicate nutrition, sour and bitter often serve as a warning signals for acidity or toxins, respectively. So how does the brain decide what’s safe to eat when it encounters a meal that’s both sweet and bitter?

Fruit flies taste and eat with their proboscis. Click here or on the image to see a video of a fruit fly eating!

To answer this question, French et al. turned to fruit flies. Like the rest of us in the animal kingdom, flies are attracted to sweet foods and avoid bitter foods, and they have taste cells in their proboscis (the fly tongue, see image). Over the past decade, fly researchers have developed quick and easy experiments to test food preferences in flies, and have even mapped the neurons corresponding to each taste modality on their proboscis, including bitter-sensing cells and sweet-sensing cells. This provided a great system to investigate how the brain decides to avoid sweet foods with a bitter aftertaste.

In flies and other animals, bitter foods activate bitter-sensing cells that cause aversion, and sweet foods activate sweet-sensing cells that cause attraction and feeding. Yet, researchers in multiple animal models had found that the presence of a bitter substance in a sweet food can suppress the eating behavior, indicating some crossover between how these flavors are represented in the brain. While this seems straightforward (you don’t want to eat something potentially deadly, even if it’s nutritious), exactly how and why the brain makes this decision was not understood. Are bitter-sensing cells suppressing sweet-sensing cells? Or do the bitter substances instead inhibit the sweet-sensing cells directly?

Interestingly, the authors of this paper discovered that bitter substances could actually inhibit the sweet-sensing cells directly. The researchers first confirmed that flies were attracted to sugar water (extending their proboscis toward it, see image), and avoided water with a bitter chemical (retracting their proboscis away from it). The authors then mixed a bitter substance into the sugar water and found that the flies quickly recoiled from the meal.

The authors hypothesized that if bitter-sensing cells themselves were suppressing sweet-sensing cell activation, then killing off the bitter-sensing cells should prevent the flies from avoiding the sugar+bitter offering. But instead, they found that the flies were still able to avoid sugar mixtures with certain bitter substances. They further investigated by recording the electrical activity of the taste neurons and found that some of the bitter substances they tested were actually interacting directly with the sweet-sensing cells to suppress their activity. This was a surprising finding, since it was previously thought that sweet-sensing cells only respond to sweet substances, bitter-sensing cells only respond to bitter, and so on.

So if bitter substances can directly suppress sugar-sensing and therefore prevent eating, why do bitter-sensing cells even need to exist? What’s the evolutionary advantage? For one, bitter chemicals may show up in other non-sweet foods that flies will need to recognize as dangerous. But even more interestingly, the researchers found that not all bitter substances could directly suppress sweet-sensing cells. For example, strychnine (a deadly pesticide) and three other bitter chemicals interacted with sweet-sensing cells, but caffeine, nicotine, and a few other bitter chemicals did not. The researchers suggest that the first group of chemicals may be much more toxic to the flies, and they therefore may have evolved a back-up system of protection from them. Thus, bitter-sensing cells are still necessary for signaling avoidance of less-toxic but still-dangerous chemicals.

Chocolate is an example of a food with conflicting signals. Theobromine, the bitter (and stimulating) chemical in chocolate, is safe in small quantities but can be dangerous in large quantities. Yet most people love the taste of chocolate. Have we evolved to recognize that the potential nutritional benefits of chocolate outweigh the risk?

This research shows that flies have developed two methods of detecting dangerous bitter substances in potential food sources. First, bitter-sensing cells are activated and signal aversion. Second, sweet-sensing cells are directly suppressed by some bitter chemicals in order to simplify the taste messages sent to the brain, which would otherwise be conflicting. Research in other animal models, including mammals, has found that they also avoid sweet foods laced with bitter chemicals, suggesting that these organisms likely use similar strategies for deciding what’s safe to eat.

So that leaves me with one remaining question: Why does chocolate taste so good?